This phase I trial tests the safety, side effects and best dose of ziftomenib with venetoclax and gemtuzumab ozogamicin for the treatment of pediatric patients with acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Ziftomenib is in a class of medications called menin inhibitors. It works by blocking the action of proteins that signal cancer cells to multiply, which may help keep cancer cells from growing. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to an antitumor antibiotic drug, called calicheamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers calicheamicin to kill them. Giving ziftomenib with venetoclax and gemtuzumab ozogamicin may be safe and tolerable in treating pediatric patients with relapsed or refractory AML or MPAL.
Additional locations may be listed on ClinicalTrials.gov for NCT06448013.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Branko Cuglievan
Phone: 713-563-1499
PRIMARY OBJECTIVE:
I. To determine the safety, tolerability, and recommended Phase II dose (RP2D) of ziftomenib in combination with gemtuzumab ozogamicin and venetoclax for pediatric patients with acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To determine the preliminary assessment of efficacy by overall response (OR), including complete remission (CR), CR with incomplete blood count recovery and partial remission, overall survival (OS), event‐free survival (EFS) and duration of response (DOR) of pediatric patients treated with this combination.
II. To determine time to first response and time to best response of pediatric patients treated with this combination.
EXPLORATORY OBJECTIVE:
I. To evaluate molecular and cellular markers that may be predictive of antitumor activity and/or resistance.
OUTLINE:
Patients receive gemtuzumab ozogamicin intravenously (IV) on day 1, venetoclax orally (PO) once per day (QD) on days 1-14, and ziftomenib PO QD on days 8-28 of cycle 1 and days 1-28 of subsequent cycles. Patients may also receive methotrexate intrathecally (IT), hydrocortisone IT and/or cytarabine IT when clinically indicated. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve at least a partial remission within 6 cycles stop treatment on study. Patients undergo bone marrow biopsy and aspiration, and blood sample collection throughout the study as well as echocardiography (ECHO) during screening.
After completion of study treatment, patients are followed up every month for up to 3 years.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorBranko Cuglievan